P181 infliximab exposure during induction associate with time to remission and disease control of inflammatory bowel disease
Laharie, D.(1)*; Rabizadeh, S.(2);D’Haens, G.(3);Dubinsky, M.(4);Panetta, J.C.(5);Everts-van der Wind, A.(6);Dreesen, E.(7);Spencer, E.(4);Vermeire, S.(8);Dervieux, T.(6);
(1)Hospital Haut-Leveque, Department of Gastroenterology and Hepatology, Pessac, France;(2)Cedars Sinai Medical Center, Gastroenterology, Los Angeles- CA, United States;(3)University of Amsterdam- AMC, Gastroenterology, Amsterdam, The Netherlands;(4)Mount Sinai Medical Center, Gastroenterology, New York- NY, United States;(5)St Jude Children’s Research Hospital, Gastroenterology, Memphis TN-, United States;(6)Prometheus, Laboratories, San Diego- CA, United States;(7)KU Leuven, Biology, Leuven, Belgium;(8)KU Leuven, Gastroenterology, Leuven, Belgium;
Background
Infliximab (IFX) exposure is established predictive factor of pharmacokinetic (PK) origin in inflammatory bowel disease, and expert consensus is to achieve adequate exposure during induction (1). We evaluated the performance of a Bayesian PK tool in IBD patients starting IFX.
Methods
Trough IFX collected immediately before the third and fourth infusion (corresponding to week 6 and 14 on a standard dosing schedule, respectively) were evaluated from 307 IBD patients starting IFX and enrolled in three cohorts of IBD. The first cohort patients was adult CD enrolled in the TAILORIX trial (n=101, mean age [SEM]: 35.0±1.4 years, 60% female) (2), a second cohort was from the PRECISION trial (n=158, mean age 15.8±0.5, 75% CD, 46% female) (3) and a third cohort consisted of pediatric patients (n=45, mean age 13.2±0.5, 71% CD, 40% female). Forecasted IFX concentration at the 4th infusion were estimated using serum IFX, antibodies to IFX and albumin determined at the third infusion using population PK calculator with Bayesian prior. The outcome variable was a CRP-based clinical remission during follow-up with CRP levels below 3 mg/L in the absence of symptoms (corresponding to remission). Sustained CRP-based clinical remission status over the maintenance period was also calculated. Statistics consisted of Kaplan Meier analysis with calculation of Hazard ratio (HR), and logistic regression.
Results
IFX concentration above 15 µg/mL before the third infusion had shorter time to CRP-based clinical remission as compared to IBD with IFX concentration below 15 µg/mL (mean followup: 182±11 days). Measured IFX concentrations above 10 µg/mL before the 4th infusion were also associated with a higher rate and shorter time to remission (p<0.01). Similar results were observed with forecasted concentration above 10 µg/mL at the 4th infusion (p<0.01). In the presence of IFX concentration above 15 µg/mL there was a 2.5-fold higher likelihood of sustained CRP based clinical remission status during maintenance as compared to IFX concentrations below 15 µg/mL (p<0.01). Forecasted IFX level above 10 µg/mL at 4th infusion associated with 3.9-fold higher likelihood of CRP-based clinical remission. (p<0.01).
Conclusion
These data further support that IFX concentrations above recommended cutoffs are best to predict enhanced disease control. Patients presenting with low forecasted exposure may benefit from dose intensification sooner than the scheduled standard infusion.
References:
(1) Cheifetz AS et al. Am J Gastroenterol. 2021 116:2014-2025. (2) D’Haens G et al., Gastroenterology. 2018 154:1343-1351. (3) Dubinsky M et al. Inflamm Bowel Dis. 2022 28:1375-1385